title: AKT1E17K mutations cluster with meningothelial and transitional meningiomas and can be detected by SFRP1 immunohistochemistry.
abstract: The activating E17K mutation in the AKT1 gene has been detected in several tumor entities. Currently several clinical studies with specific AKT1 inhibitors are under way. To determine whether AKT1 mutations are involved in human tumors of the nervous system, we examined a series of 1,437 tumors including 391 primary intracranial brain tumors and 1,046 tumors of the coverings of the central and peripheral nervous system. AKT1E17K mutations were exclusively seen in meningiomas and occurred in 65 of 958 of these tumors. A strong preponderance was seen in the variant of meningothelial meningioma WHO grade I of basal and spinal localization. In contrast, AKT1E17K mutations were rare in WHO grade II and absent in WHO grade III meningiomas. In order to more effectively detect this mutation, we tested for immunohistochemical markers associated with this alteration. We observed strong up-regulation of SFRP1 expression in all meningiomas with AKT1E17K mutation and in HEK293 cells after transfection with mutant AKT1E17K, but not in meningiomas and HEK293 cells lacking this mutation.
authors.affiliation: Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, INF 224, 69120, Heidelberg, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Sahm
authors.forename: Juliane
authors.initials: J
authors.lastname: Bissel
authors.forename: Christian
authors.initials: C
authors.lastname: Koelsche
authors.forename: Leonille
authors.initials: L
authors.lastname: Schweizer
authors.forename: David
authors.initials: D
authors.lastname: Capper
authors.forename: David
authors.initials: D
authors.lastname: Reuss
authors.forename: Katja
authors.initials: K
authors.lastname: Böhmer
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lass
authors.forename: Tanja
authors.initials: T
authors.lastname: Göck
authors.forename: Katrin
authors.initials: K
authors.lastname: Kalis
authors.forename: Jochen
authors.initials: J
authors.lastname: Meyer
authors.forename: Antje
authors.initials: A
authors.lastname: Habel
authors.forename: Stefanie
authors.initials: S
authors.lastname: Brehmer
authors.forename: Michel
authors.initials: M
authors.lastname: Mittelbronn
authors.forename: David T W
authors.initials: DT
authors.lastname: Jones
authors.forename: Jens
authors.initials: J
authors.lastname: Schittenhelm
authors.forename: Steffi
authors.initials: S
authors.lastname: Urbschat
authors.forename: Ralf
authors.initials: R
authors.lastname: Ketter
authors.forename: Stephanie
authors.initials: S
authors.lastname: Heim
authors.forename: Christian
authors.initials: C
authors.lastname: Mawrin
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Hainfellner
authors.forename: Anna-Sophie
authors.initials: AS
authors.lastname: Berghoff
authors.forename: Matthias
authors.initials: M
authors.lastname: Preusser
authors.forename: Albert
authors.initials: A
authors.lastname: Becker
authors.forename: Christel
authors.initials: C
authors.lastname: Herold-Mende
authors.forename: Andreas
authors.initials: A
authors.lastname: Unterberg
authors.forename: Christian
authors.initials: C
authors.lastname: Hartmann
authors.forename: Philipp
authors.initials: P
authors.lastname: Kickingereder
authors.forename: V Peter
authors.initials: VP
authors.lastname: Collins
authors.forename: Stefan M
authors.initials: SM
authors.lastname: Pfister
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D004252:DNA Mutational Analysis; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008577:Meningeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008579:Meningioma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D060787:Neoplasm Grading; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D000094742:Secreted Frizzled-Related Proteins
chemical_list: D014408:Biomarkers, Tumor; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051057:Proto-Oncogene Proteins c-akt; C117636:SFRP1 protein, human; D000094742:Secreted Frizzled-Related Proteins; C494918:AKT1 protein, human